Pneumococcal (PNC)-induced pulmonary leukostasis and granulocytopenia might contribute to the morbidity and mortality associated with PNC disease. PNC sonicate will be intravenously injected into NZW rabbits and blood samples obtained immediately prior to and at varying intervals post-injection. Measurements of granulocytes, complement components, and PNC capsular antigen will be made. At times of profound neutropenia, animals will be sacrificied and lungs fixed in situ to histologically quantitate pulmonary granulocyte sequestration. Modifications of this basic model will be introduced to address specific questions. Sterile autologous/heterologous serum/plasma exposed in vitro-in vivo to PNC constituents will be infused into normal animals. If granulocytopenia and pulmonary leukostasis prove transferrable, a responsible serum/plasma factor(s) will be sought and characterized. PNC sonicate will be injected into congenitally complement deficient and/or complement-depleted animals using cobre venom factor to establish a role for complement derived products. (3H)-Thymidine labeled granulocytes will be infused into animals to be challenged with PNC sonicate and radioactive counts performed on various tissues. This will confirm and better quantitate the previously noted PNC-induced pulmonary granulocyte sequestration and determine the scope of the leukostatic process in extra-pulmonary foci. Pulmonary functions including alveolo-arterial O2 gradients and pulmonary artery resistances will be studied in normal and granulocyte-depleted animals. This might characterize any pulmonary dysfunction and confirm the role of granulocytes in its pathogenesis. Bronchoalveolar lavage fluids from animals displaying pulmonary leukostasis will be collected to test for alveolar macrophage-derived chemotactic factor, possibly responsible for localizing granulocytes in the lungs. Attempts will be made to prevent, abort or ameliorate PNC-induced pulmonary leukostasis with various pharmacological agents known to modify granulocyte adherence and aggregation and/or to interfere with activation of the complement system.